This project is centered on the study of the autologous mixed lymphocyte reaction (AMLR), the proliferative response of T cells brought about by exposure to autologous B cells or macrophages. In the previous period we generated autoreactive T cell lines by repeatedly stimulating T cells with autologous non-T cells (B cells and macrophages) in the presence of IL-2. We showed that such lines respond to autologous but not allogeneic cells and, in addition, do not respond to mitogens and representative antigens. A key finding was that the lines were comprised of two sub-populations which bore the Leu 2 or the Leu 3 antigens; the former (Leu 2-positive) population mediated NK-like cytotoxicity, whereas the latter (Leu 3-positive) population were capable of killing autologous B cells. These studies thus raised the possibility that autoreactive cells may participate in autoimmune reactions. In the present series of studies we determined the immunoregulatory activity of an autoreactive T cell lines and clones. In particular, we derived a cloned T cell line by the limiting dilution method from a continously growing "bulk" cell line. The cloned cell was OKT4 positive but was nevertheless a suppressor T cell in that it suppressed Ig production by indicator cultures of fresh T cells (and B cells stimulated by pokeweed mitogen. The suppressor acitvity was exerted directly on B cells since it was observed in cultures of B cells stimulated by EB virus in the absence of T cells. The T4 suppressor cell line was a suppressor-effect population in that it suppressed in the absence of added OKT8-positive cells. Finally, the T4 suppressor cell line elaborated a factor which inhibits Ig synthesis at low concentrations. These studies indicate that suppressor cells are generated during the autologous MLR which are OKT4-positive. These regulatory cells address B cell function directly and may thus have a particular role in the pathogenesis of autoimmunity and in the B cell hyperreactivity observed in patients with AIDS.